Humanitas Clinical and Research Center, Italy
Posters & Accepted Abstracts: Immunome Res
Primary biliary cirrhosis (PBC) is a liver specific autoimmune disease (AD) characterized by selective destruction of biliary epithelial cells (BEC) and anti-mitochondrial antibodies (AMA). Numerous studies suggest that PBC ensues from a multilineage T and B cell response against the main mitochondrial autoantigen, the E2 component of the pyruvate dehydrogenase (PDC-E2). PBC is often considered a model AD due to the homogeneity of patients and the high specificity of AMA. A major void in the bridge from the loss of tolerance to clinical pathology in PBC is the enigmatic observation that while mitochondria are found in all cells, only small BECs are destroyed. We have recently demonstrated that following apoptosis human BECs translocate PDC-E2 immunologically intact into the apoptotic bodies. Further, we have shown the critical requirement of monocyte derived macrophages (MDMf), from patients with PBC to produce pro-inflammatory cytokines in response to biliary apotopes in the presence of AMAs. ADs affect almost 5% of the western population and have great impact on the quality of life. Our understanding of organ specific AD, including PBC, is compromised by lack of mechanistic understanding as to how specific organ damage occurs. We are addressing a key question for autoimmunity with the overall objective of identifying therapeutic targets for PBC: indeed, strong evidence suggests that impairment in the uptake of apoptotic debris leads to the development of AD.